Pub Date : 2026-05-01Epub Date: 2025-12-05DOI: 10.1016/j.jhlto.2025.100457
Mohammad U. Ahmed , Michael Dickinson , David Fermin , Milena Jani , Eesha Purohit , Matthew Gonzalez , Ryan Grayburn , Sangjin Lee , Nabin K. Shrestha , Dana Marsy , Robert Hooker , Erin McNeely , Richard C. Sadler , Renzo Y. Loyaga-Rendon MD. MSPH, PhD.
Background
The OPTN heart transplant allocation policy implemented in 2018 led to significant improvements in waitlist outcomes, but disparities persist. Our study evaluated the effect of the implementation of the new allocation on waitlist and post-transplantation outcomes in rural versus urban communities.
Methods
Patients registered for HT in the OPTN database between January 1, 2014, and December 31, 2021, were included as rural or urban according to ZIP code. The cumulative incidence (CI) of death/delisting and transplantation in the different allocations were calculated. Post-transplant survival was calculated using Kaplan-Meier methodology.
Results
26,450 patients were listed for transplant. Rural residents were more commonly white and had a higher incidence of ischemic cardiomyopathy. Both allocations saw a similar decrease in the CI of death/delisting from the wait list and an increase in the CI of HT in both rural and urban communities. In the prior allocation, no differences existed in the CI of death/delisting or transplantation between rural and urban residents. In the current allocation, rural residents had a higher frequency of death/delisting (p=0.01) after adjusting for risk factors. No differences existed in the CI of transplantation or post-transplant survival.
Conslusions
Our findings suggest that despite an overall decrease in CI of death/delisting in both rural and urban communities, rural residence is associated with a disproportionately higher CI of death/delisting on the transplant list in the current allocation. We found no differences in the CI of transplantation or survival after transplant.
{"title":"Waitlist and post-transplant outcomes in rural communities with the current heart transplant allocation","authors":"Mohammad U. Ahmed , Michael Dickinson , David Fermin , Milena Jani , Eesha Purohit , Matthew Gonzalez , Ryan Grayburn , Sangjin Lee , Nabin K. Shrestha , Dana Marsy , Robert Hooker , Erin McNeely , Richard C. Sadler , Renzo Y. Loyaga-Rendon MD. MSPH, PhD.","doi":"10.1016/j.jhlto.2025.100457","DOIUrl":"10.1016/j.jhlto.2025.100457","url":null,"abstract":"<div><h3>Background</h3><div>The OPTN heart transplant allocation policy implemented in 2018 led to significant improvements in waitlist outcomes, but disparities persist. Our study evaluated the effect of the implementation of the new allocation on waitlist and post-transplantation outcomes in rural versus urban communities.</div></div><div><h3>Methods</h3><div>Patients registered for HT in the OPTN database between January 1, 2014, and December 31, 2021, were included as rural or urban according to ZIP code. The cumulative incidence (CI) of death/delisting and transplantation in the different allocations were calculated. Post-transplant survival was calculated using Kaplan-Meier methodology.</div></div><div><h3>Results</h3><div>26,450 patients were listed for transplant. Rural residents were more commonly white and had a higher incidence of ischemic cardiomyopathy. Both allocations saw a similar decrease in the CI of death/delisting from the wait list and an increase in the CI of HT in both rural and urban communities. In the prior allocation, no differences existed in the CI of death/delisting or transplantation between rural and urban residents. In the current allocation, rural residents had a higher frequency of death/delisting (p=0.01) after adjusting for risk factors. No differences existed in the CI of transplantation or post-transplant survival.</div></div><div><h3>Conslusions</h3><div>Our findings suggest that despite an overall decrease in CI of death/delisting in both rural and urban communities, rural residence is associated with a disproportionately higher CI of death/delisting on the transplant list in the current allocation. We found no differences in the CI of transplantation or survival after transplant.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"12 ","pages":"Article 100457"},"PeriodicalIF":0.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146190264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-05DOI: 10.1016/j.jhlto.2025.100454
Carolin Steinack , Macé M. Schuurmans , Silvan M. Vesenbeckh , René Hage , Zsofia Rosselli , Silvia Ulrich , Malcolm Kohler , Jan Rüschoff , Martina Haberecker , Maurice Roeder , Thomas Gaisl
Introduction
Donor-derived cell-free DNA (dd-cfDNA) may be a promising biomarker for detecting acute cellular rejection (ACR) in lung transplant recipients (LTR) without the need for invasive transbronchial biopsies. We aimed to validate a clinical plasma dd-cfDNA assay for the detection of ACR, as determined by cryobiopsy, and to assess its clinical utility.
Methods
In this prospective cohort, dd-cfDNA fraction was measured using a novel single-nucleotide polymorphism-based assay in LTR undergoing surveillance bronchoscopy with cryobiopsies 2, 4, 6, and 12 months after transplantation (and when indicated). Performance characteristics were calculated for LTR without ACR and LTR with ACR (defined as ACR based on pathological assessment of the cryobiopsies ≥A1).
Results
The incidence of ACR (A1 (N = 2), grade A2 (N = 3), grade A3 (N = 1), and no grade A4 or antibody-mediated rejection) was 14% in 43 samples of 39 LTR. The median dd-cfDNA fraction was similar for the stable cohort and the cohort with ACR (median 0.41% [0.15% to 0.72%] vs. 0.56% [0.10% to 3.07%], p = 0.630). The area under the receiver operator characteristic curve for ACR was 59.3% (95% CI 38.3% to 80.3%). Using a ≥1% dd-cfDNA fraction threshold (≥0.5% for single lung transplantations), the negative predictive value for ACR was 87.9% (95% CI 74.1% to 97.6%), and the positive predictive value was 20.0% (95% CI 8.0% to 32.0%). In the sensitivity analysis, altering the ACR category (≥A1 vs. ≥A2) or the dd-cfDNA threshold >0.85% did not produce significant changes in the outcomes.
Conclusions
The incidence of ACR (≥A1 or ≥A2) did not appear to be closely associated with the fraction of dd-cfDNA. More research with a larger sample size and long-term follow-up is needed to evaluate the association between dd-cfDNA and ACR incidence detected by cryobiopsy.
{"title":"Correlation between acute cellular rejection detected with cryobiopsy and elevated dd-cfDNA in lung transplant recipients","authors":"Carolin Steinack , Macé M. Schuurmans , Silvan M. Vesenbeckh , René Hage , Zsofia Rosselli , Silvia Ulrich , Malcolm Kohler , Jan Rüschoff , Martina Haberecker , Maurice Roeder , Thomas Gaisl","doi":"10.1016/j.jhlto.2025.100454","DOIUrl":"10.1016/j.jhlto.2025.100454","url":null,"abstract":"<div><h3>Introduction</h3><div>Donor-derived cell-free DNA (dd-cfDNA) may be a promising biomarker for detecting acute cellular rejection (ACR) in lung transplant recipients (LTR) without the need for invasive transbronchial biopsies. We aimed to validate a clinical plasma dd-cfDNA assay for the detection of ACR, as determined by cryobiopsy, and to assess its clinical utility.</div></div><div><h3>Methods</h3><div>In this prospective cohort, dd-cfDNA fraction was measured using a novel single-nucleotide polymorphism-based assay in LTR undergoing surveillance bronchoscopy with cryobiopsies 2, 4, 6, and 12 months after transplantation (and when indicated). Performance characteristics were calculated for LTR without ACR and LTR with ACR (defined as ACR based on pathological assessment of the cryobiopsies ≥A1).</div></div><div><h3>Results</h3><div>The incidence of ACR (A1 (N = 2), grade A2 (N = 3), grade A3 (N = 1), and no grade A4 or antibody-mediated rejection) was 14% in 43 samples of 39 LTR. The median dd-cfDNA fraction was similar for the stable cohort and the cohort with ACR (median 0.41% [0.15% to 0.72%] vs. 0.56% [0.10% to 3.07%], <em>p</em> = 0.630). The area under the receiver operator characteristic curve for ACR was 59.3% (95% CI 38.3% to 80.3%). Using a ≥1% dd-cfDNA fraction threshold (≥0.5% for single lung transplantations), the negative predictive value for ACR was 87.9% (95% CI 74.1% to 97.6%), and the positive predictive value was 20.0% (95% CI 8.0% to 32.0%). In the sensitivity analysis, altering the ACR category (≥A1 vs. ≥A2) or the dd-cfDNA threshold >0.85% did not produce significant changes in the outcomes.</div></div><div><h3>Conclusions</h3><div>The incidence of ACR (≥A1 or ≥A2) did not appear to be closely associated with the fraction of dd-cfDNA. More research with a larger sample size and long-term follow-up is needed to evaluate the association between dd-cfDNA and ACR incidence detected by cryobiopsy.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100454"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145839589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-30DOI: 10.1016/j.jhlto.2025.100477
Elizabeth Silver , Kimberly N. Hong MD, MHSA , Hao A. Tran MD , Victor Pretorius MBchB , Mark J. Kearns MD , Marcus A. Urey MD , Eric D. Adler MD , Quan M. Bui MD
Background
Left ventricular assist device (LVAD) implantation is a life-saving therapy for end-stage heart failure, but right ventricular failure (RVF) remains a major complication. Current RVF risk models are limited. We hypothesized that pathogenic/likely pathogenic (P/LP) variants increase intrinsic RV vulnerability and post-LVAD RVF risk.
Methods and Results
In a single-center retrospective study of 136 adults undergoing LVAD implantation in 2018–2024, 87% were male, 65% non-White, and 68% had non-ischemic cardiomyopathy. Genetic testing was completed in 48 (35%), identifying P/LP variants in 19%. Patients with P/LP variants had higher early RVF rates (89% vs. 38% vs. 15%, p<0.01) and longer hospitalizations (84 vs. 31 vs. 24 days, p=0.02) than those with variants of uncertain significance or negative results. Outcomes did not differ by ischemic versus non-ischemic etiology.
Conclusions
P/LP variants were associated with early RVF, suggesting that genetic testing may inform RVF risk stratification and perioperative management.
{"title":"Association between genetics variants and clinical outcomes in patients with left ventricular assist device","authors":"Elizabeth Silver , Kimberly N. Hong MD, MHSA , Hao A. Tran MD , Victor Pretorius MBchB , Mark J. Kearns MD , Marcus A. Urey MD , Eric D. Adler MD , Quan M. Bui MD","doi":"10.1016/j.jhlto.2025.100477","DOIUrl":"10.1016/j.jhlto.2025.100477","url":null,"abstract":"<div><h3>Background</h3><div>Left ventricular assist device (LVAD) implantation is a life-saving therapy for end-stage heart failure, but right ventricular failure (RVF) remains a major complication. Current RVF risk models are limited. We hypothesized that pathogenic/likely pathogenic (P/LP) variants increase intrinsic RV vulnerability and post-LVAD RVF risk.</div></div><div><h3>Methods and Results</h3><div>In a single-center retrospective study of 136 adults undergoing LVAD implantation in 2018–2024, 87% were male, 65% non-White, and 68% had non-ischemic cardiomyopathy. Genetic testing was completed in 48 (35%), identifying P/LP variants in 19%. Patients with P/LP variants had higher early RVF rates (89% vs. 38% vs. 15%, <em>p</em><0.01) and longer hospitalizations (84 vs. 31 vs. 24 days, p=0.02) than those with variants of uncertain significance or negative results. Outcomes did not differ by ischemic versus non-ischemic etiology.</div></div><div><h3>Conclusions</h3><div>P/LP variants were associated with early RVF, suggesting that genetic testing may inform RVF risk stratification and perioperative management.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100477"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146026193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-08DOI: 10.1016/j.jhlto.2026.100484
Hui Zhen Lo , Louise Fuller , Peter Bergin , Caitlin Cheshire , Sarah Gutman , James Hare , David M. Kaye , Hitesh Patel , Janelle Mclean , Julia Rix , Andrew J. Taylor
Background
In patients with advanced heart failure, it is assumed that orthotopic heart transplant (OHTx) results in greater exercise capacity compared to ventricular assist device (VAD), however this has not been formally examined. In this study, we evaluated the exercise capacity of patients following VAD and OHTx after a structured outpatient rehabilitation program.
Methods
We performed a retrospective single-center cohort study of patients undergoing OHTx or VAD at a tertiary centre from January 2022 to January 2024. Comorbidities and the option of either intervention was used as inputs in a multivariate linear regression model for prediction of 3-month 6-minute walk test (6MWT). Major factors identified were added as covariates in the combined cohort to determine predictors of 6MWT.
Results
A total of 78 patients were included. The maximal recorded 6MWT was similar between both cohorts (median 6MWT OHTx: 534.0 (478.8-600.3)m; VAD: 608.5 (487.0-643.5)m, p=0.30). Gender was a significant predictor of 6MWT in the OHTx cohort (β=-69.1, p<0.02) with a strong trend in the VAD cohort (β=-199, p<0.09). VAD was not predictive of 3-month 6MWT (p=0.99) in OHTx patients bridged with VAD. VAD or OHTx was also not predictive of 6MWT (p=0.88) while total length of stay was a significant predictor of 6MWT (p<0.0001) in the combined cohort.
Conclusions
In patients with advanced heart failure, VAD and OHTx are associated with a similar level of exercise capacity and does not impact exercise capacity in patients undergoing OHTx who are bridged with a VAD. In patients with OHTx, gender was the strongest predictor of exercise capacity.
{"title":"Exercise capacity after mechanical circulatory support compared to heart transplant in advanced heart failure","authors":"Hui Zhen Lo , Louise Fuller , Peter Bergin , Caitlin Cheshire , Sarah Gutman , James Hare , David M. Kaye , Hitesh Patel , Janelle Mclean , Julia Rix , Andrew J. Taylor","doi":"10.1016/j.jhlto.2026.100484","DOIUrl":"10.1016/j.jhlto.2026.100484","url":null,"abstract":"<div><h3>Background</h3><div>In patients with advanced heart failure, it is assumed that orthotopic heart transplant (OHTx) results in greater exercise capacity compared to ventricular assist device (VAD), however this has not been formally examined. In this study, we evaluated the exercise capacity of patients following VAD and OHTx after a structured outpatient rehabilitation program.</div></div><div><h3>Methods</h3><div>We performed a retrospective single-center cohort study of patients undergoing OHTx or VAD at a tertiary centre from January 2022 to January 2024. Comorbidities and the option of either intervention was used as inputs in a multivariate linear regression model for prediction of 3-month 6-minute walk test (6MWT). Major factors identified were added as covariates in the combined cohort to determine predictors of 6MWT.</div></div><div><h3>Results</h3><div>A total of 78 patients were included. The maximal recorded 6MWT was similar between both cohorts (median 6MWT OHTx: 534.0 (478.8-600.3)m; VAD: 608.5 (487.0-643.5)m, <em>p</em>=0.30). Gender was a significant predictor of 6MWT in the OHTx cohort (β=-69.1, <em>p</em><0.02) with a strong trend in the VAD cohort (β=-199, <em>p</em><0.09). VAD was not predictive of 3-month 6MWT (<em>p</em>=0.99) in OHTx patients bridged with VAD. VAD or OHTx was also not predictive of 6MWT (<em>p</em>=0.88) while total length of stay was a significant predictor of 6MWT (<em>p</em><0.0001) in the combined cohort.</div></div><div><h3>Conclusions</h3><div>In patients with advanced heart failure, VAD and OHTx are associated with a similar level of exercise capacity and does not impact exercise capacity in patients undergoing OHTx who are bridged with a VAD. In patients with OHTx, gender was the strongest predictor of exercise capacity.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100484"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146076770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-14DOI: 10.1016/j.jhlto.2025.100409
Felix Riunga MD , Carlos Cervera MD, PhD , Dima Kabbani MD, MSc
Solid organ transplantation (SOT) is the definitive treatment for end-stage organ disease but also introduces a heightened risk of infection in the post-transplant period. In heart and lung transplantation, unique factors predisposing to infection include exposure of the lungs to the external environment, alteration of airway anatomy, pretransplant infection and colonization with difficult-to-treat organisms, and pretransplant presence of infected devices. This is in addition to risks common to all SOT leading, including immunosuppression. The aim of pretransplant infectious disease screening in SOT recipients is to prospectively identify infectious risks through careful history taking, examination, and laboratory testing, as well as mitigating these risks through vaccination, treatment, prophylaxis, and counseling on safe living. In this article, we review infectious risks in heart and lung transplant candidates and discuss recommendations for screening before transplantation.
{"title":"Pretransplant screening for infections in lung and heart transplant candidates","authors":"Felix Riunga MD , Carlos Cervera MD, PhD , Dima Kabbani MD, MSc","doi":"10.1016/j.jhlto.2025.100409","DOIUrl":"10.1016/j.jhlto.2025.100409","url":null,"abstract":"<div><div>Solid organ transplantation (SOT) is the definitive treatment for end-stage organ disease but also introduces a heightened risk of infection in the post-transplant period. In heart and lung transplantation, unique factors predisposing to infection include exposure of the lungs to the external environment, alteration of airway anatomy, pretransplant infection and colonization with difficult-to-treat organisms, and pretransplant presence of infected devices. This is in addition to risks common to all SOT leading, including immunosuppression. The aim of pretransplant infectious disease screening in SOT recipients is to prospectively identify infectious risks through careful history taking, examination, and laboratory testing, as well as mitigating these risks through vaccination, treatment, prophylaxis, and counseling on safe living. In this article, we review infectious risks in heart and lung transplant candidates and discuss recommendations for screening before transplantation.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100409"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-03DOI: 10.1016/j.jhlto.2025.100425
Erik L. Frandsen , Natalie S. Shwaish , Richard E. Chinnock
The control of linear growth from fetal life through adolescence is complex and variable. Many factors, intrinsic and extrinsic, can affect growth at all stages of transplant. In this review, we highlight the normal process of linear growth. We describe factors affecting growth before heart transplant and review the typical patterns of growth after transplant. We review ways to optimize growth during all stages of transplantation, and finally we highlight the limited experience with recombinant human growth hormone in heart and other solid organ transplants.
{"title":"Growth in pediatric heart transplantation","authors":"Erik L. Frandsen , Natalie S. Shwaish , Richard E. Chinnock","doi":"10.1016/j.jhlto.2025.100425","DOIUrl":"10.1016/j.jhlto.2025.100425","url":null,"abstract":"<div><div>The control of linear growth from fetal life through adolescence is complex and variable. Many factors, intrinsic and extrinsic, can affect growth at all stages of transplant. In this review, we highlight the normal process of linear growth. We describe factors affecting growth before heart transplant and review the typical patterns of growth after transplant. We review ways to optimize growth during all stages of transplantation, and finally we highlight the limited experience with recombinant human growth hormone in heart and other solid organ transplants.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100425"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-03DOI: 10.1016/j.jhlto.2025.100446
André A. Scussel , Fabiana G. Marcondes-Braga , Cristhian V. Espinoza Romero, Daniel C. de Marchi, Mônica Samuel Ávila Grinberg, Fernanda Barone Alves do Santos, Ana Maria Peixoto Cardoso Duque, Sandrigo Mangini, Luís Fernando Bernal Seguro, Iáscara Wozniak Campos, Fabio Gaiotto, Fernando Bacal
Background
Biomarkers for acute rejection diagnosis are frequently searched, and data from medical literature are conflicting. The role of high-sensitivity troponin I in the diagnosis of acute cellular rejection (ACR) after heart transplant (HT) is uncertain. However, it is a widely used and accessible tool in developing countries.
Objective
This study aims to determine whether hs-TnI can serve as a reliable and accessible tool to identify patients with clinically significant rejection (ACR >2R) in a real-world Latin American cohort that has different etiologies than the epidemiology of the main trials.
Methods
In this retrospective cohort, we evaluated data from electronic records of HT recipients submitted to HT from March, 2020 to September, 2022 using REdCAp database. All patients who underwent endomyocardial biopsies (EMB) between 3 months and 2 years of HT and had samples of HS-troponin I previously measured were included in this study. The HS-troponin levels were compared between patients with ACR higher or lower than 2R.
Results
In this analysis, we included data from 187 biopsies performed at least 3 months after HT in 94 recipients who had paired Hs-troponin I samples collected. Fifty-four (57%) were men, and their median age at heart transplant was 48 ±11 years. The median hs-TnI levels were 29 (11-118) ng/L. ACR > 2R was observed in 48 EMB and the median hs-TnI levels were 69 (26-224) ng/L, which was significantly higher than levels observed in patients with grade 0R/1R [21 (9-64) ng/L, p<0.001]. The ROC curve of hs-TnI shows an AUC of 0.705; p<0.001 for the diagnosis of ACR > 2R. A cutoff of 19 ng/L showed a sensitivity of 88% and specificity of 49%, with a negative predictive value of 92%. Among biopsies from patients with Chagas disease (36.9% of the sample), hs-TnI also showed significant discriminatory power for ACR >2R (p = 0.037).
Conclusion
In this cohort, HS-troponin I was able to identify patients with acute cellular rejection. This is the largest Latin American cohort assessing hs-TnI after HT, and the first to explore its performance across specific etiologies, including Chagas disease. Prospective studies may confirm the role of HS-troponin I as a biomarker of acute rejection.
{"title":"The role of high-sensitivity troponin in identifying patients with cardiac allograft rejection","authors":"André A. Scussel , Fabiana G. Marcondes-Braga , Cristhian V. Espinoza Romero, Daniel C. de Marchi, Mônica Samuel Ávila Grinberg, Fernanda Barone Alves do Santos, Ana Maria Peixoto Cardoso Duque, Sandrigo Mangini, Luís Fernando Bernal Seguro, Iáscara Wozniak Campos, Fabio Gaiotto, Fernando Bacal","doi":"10.1016/j.jhlto.2025.100446","DOIUrl":"10.1016/j.jhlto.2025.100446","url":null,"abstract":"<div><h3>Background</h3><div>Biomarkers for acute rejection diagnosis are frequently searched, and data from medical literature are conflicting. The role of high-sensitivity troponin I in the diagnosis of acute cellular rejection (ACR) after heart transplant (HT) is uncertain. However, it is a widely used and accessible tool in developing countries.</div></div><div><h3>Objective</h3><div>This study aims to determine whether hs-TnI can serve as a reliable and accessible tool to identify patients with clinically significant rejection (ACR >2R) in a real-world Latin American cohort that has different etiologies than the epidemiology of the main trials.</div></div><div><h3>Methods</h3><div>In this retrospective cohort, we evaluated data from electronic records of HT recipients submitted to HT from March, 2020 to September, 2022 using REdCAp database. All patients who underwent endomyocardial biopsies (EMB) between 3 months and 2 years of HT and had samples of HS-troponin I previously measured were included in this study. The HS-troponin levels were compared between patients with ACR higher or lower than 2R.</div></div><div><h3>Results</h3><div>In this analysis, we included data from 187 biopsies performed at least 3 months after HT in 94 recipients who had paired Hs-troponin I samples collected. Fifty-four (57%) were men, and their median age at heart transplant was 48<!--> <!-->±11 years. The median hs-TnI levels were 29 (11-118) ng/L. ACR > 2R was observed in 48 EMB and the median hs-TnI levels were 69 (26-224) ng/L, which was significantly higher than levels observed in patients with grade 0R/1R [21 (9-64) ng/L, <em>p</em><0.001]. The ROC curve of hs-TnI shows an AUC of 0.705; <em>p</em><0.001 for the diagnosis of ACR > 2R. A cutoff of 19<!--> <!-->ng/L showed a sensitivity of 88% and specificity of 49%, with a negative predictive value of 92%. Among biopsies from patients with Chagas disease (36.9% of the sample), hs-TnI also showed significant discriminatory power for ACR >2R (<em>p</em> = 0.037).</div></div><div><h3>Conclusion</h3><div>In this cohort, HS-troponin I was able to identify patients with acute cellular rejection. This is the largest Latin American cohort assessing hs-TnI after HT, and the first to explore its performance across specific etiologies, including Chagas disease. Prospective studies may confirm the role of HS-troponin I as a biomarker of acute rejection.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100446"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145790212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-16DOI: 10.1016/j.jhlto.2025.100413
Jérémie Guillemin MD , Michael Cutrone DO , Suraj Yalamuri MD , Monica Arndt MD , Adrien Bouglé MD, PhD , Sharon L. McCartney MD, FASE
Background
Primary graft dysfunction (PGD) remains a leading cause of early morbidity and mortality after heart and lung transplantation. It results from a multifactorial process involving ischemia–reperfusion injury, inflammatory and immune responses, and donor-, recipient-, and procedural factors. Despite advances in perioperative management, PGD continues to adversely affect both short- and long-term transplant outcomes.
Methods
This narrative review synthesizes contemporary evidence and consensus recommendations from the International Society for Heart and Lung Transplantation (ISHLT) and recent clinical studies to delineate perioperative strategies aimed at preventing PGD in heart and lung transplantation. Focus areas include donor and recipient optimization, organ preservation strategies, intraoperative management, and emerging perfusion technologies.
Results
In heart transplantation, modifiable factors such as pre-transplant amiodarone exposure and donor–recipient mismatch increase PGD risk. Among preservation methods, hypothermic oxygenated perfusion has demonstrated reductions in PGD incidence, while controlled hypothermia has been associated with reduced PGD rates in observational studies. Normothermic ex vivo perfusion has shown improved graft preservation. In lung transplantation, the use of low-potassium dextran preservation solutions is associated with lower PGD rates. Ex vivo lung perfusion improves allograft utilization and may reduce PGD incidence. Implantation techniques such as off-pump lung transplantation or veno-arterial extracorporeal membrane oxygenation, rather than cardiopulmonary bypass, have been associated with lower PGD rates.
Conclusions
Every step of the transplant process is important in reducing the risk of PGD. Emerging machine perfusion technologies represent a promising advancement to enhance graft utilization, reduce PGD incidence, and improve overall outcomes following heart and lung transplantation.
{"title":"Primary graft dysfunction prevention strategies in the perioperative period","authors":"Jérémie Guillemin MD , Michael Cutrone DO , Suraj Yalamuri MD , Monica Arndt MD , Adrien Bouglé MD, PhD , Sharon L. McCartney MD, FASE","doi":"10.1016/j.jhlto.2025.100413","DOIUrl":"10.1016/j.jhlto.2025.100413","url":null,"abstract":"<div><h3>Background</h3><div>Primary graft dysfunction (PGD) remains a leading cause of early morbidity and mortality after heart and lung transplantation. It results from a multifactorial process involving ischemia–reperfusion injury, inflammatory and immune responses, and donor-, recipient-, and procedural factors. Despite advances in perioperative management, PGD continues to adversely affect both short- and long-term transplant outcomes.</div></div><div><h3>Methods</h3><div>This narrative review synthesizes contemporary evidence and consensus recommendations from the International Society for Heart and Lung Transplantation (ISHLT) and recent clinical studies to delineate perioperative strategies aimed at preventing PGD in heart and lung transplantation. Focus areas include donor and recipient optimization, organ preservation strategies, intraoperative management, and emerging perfusion technologies.</div></div><div><h3>Results</h3><div>In heart transplantation, modifiable factors such as pre-transplant amiodarone exposure and donor–recipient mismatch increase PGD risk. Among preservation methods, hypothermic oxygenated perfusion has demonstrated reductions in PGD incidence, while controlled hypothermia has been associated with reduced PGD rates in observational studies. Normothermic ex vivo perfusion has shown improved graft preservation. In lung transplantation, the use of low-potassium dextran preservation solutions is associated with lower PGD rates. Ex vivo lung perfusion improves allograft utilization and may reduce PGD incidence. Implantation techniques such as off-pump lung transplantation or veno-arterial extracorporeal membrane oxygenation, rather than cardiopulmonary bypass, have been associated with lower PGD rates.</div></div><div><h3>Conclusions</h3><div>Every step of the transplant process is important in reducing the risk of PGD. Emerging machine perfusion technologies represent a promising advancement to enhance graft utilization, reduce PGD incidence, and improve overall outcomes following heart and lung transplantation.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100413"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-04DOI: 10.1016/j.jhlto.2026.100480
Bianca S. Costa MS , Bruna C. Coelho MS , Iago T.C. Grillo MD , Rachid Eduardo Noleto da Nobrega Oliveira MD, MSc , Tulio Caldonazo MD, MSc , Felipe S. Passos MD , Erlon de Avila Carvalho MD, PhD
Background
Lung transplantation is the definitive therapy for end-stage lung disease, but donor shortages contribute to high waiting list mortality. Donation after circulatory death (DCD) expands the donor pool, and ex vivo lung perfusion (EVLP) enables graft assessment and optimization. However, its impact in this setting remains uncertain. This meta-analysis aimed to evaluate whether EVLP in DCD lungs affects graft function and short-term outcomes compared with direct transplantation.
Methods
Three databases were searched. The main outcome was grade 3 primary graft dysfunction (PGD). Additional outcomes included intensive care unit (ICU) and hospital length of stay (LOS), both analyzed quantitatively. Outcomes assessed qualitatively comprised short-term survival, pneumonia, and acute rejection. Random-effects models were applied to quantitative analyses.
Results
Five observational studies (654 patients) were included. The incidence of grade 3 PGD was comparable between EVLP and non-EVLP groups (RR 1.29; 95%CI 0.97 to 1.71; p = 0.08; I² = 12.63%). Similarly, ICU LOS (p = 0.12) and hospital LOS (p = 0.83) were also comparable. Qualitative assessment showed no apparent differences in short- and mid-term survival or in the frequency of pneumonia and acute rejection between groups.
Conclusion
EVLP in DCD lung transplantation was not associated with significant differences in grade 3 PGD, ICU or hospital LOS, or short- to mid-term outcomes compared with direct transplantation. Given its time and resource demands, EVLP may not be necessary for all DCD grafts; however, it remains particularly valuable for evaluating uncertain-quality lungs, where its selective use can help ensure graft safety.
{"title":"Ex vivo lung perfusion in donation after circulatory death lung transplantation: A systematic review and meta-analysis","authors":"Bianca S. Costa MS , Bruna C. Coelho MS , Iago T.C. Grillo MD , Rachid Eduardo Noleto da Nobrega Oliveira MD, MSc , Tulio Caldonazo MD, MSc , Felipe S. Passos MD , Erlon de Avila Carvalho MD, PhD","doi":"10.1016/j.jhlto.2026.100480","DOIUrl":"10.1016/j.jhlto.2026.100480","url":null,"abstract":"<div><h3>Background</h3><div>Lung transplantation is the definitive therapy for end-stage lung disease, but donor shortages contribute to high waiting list mortality. Donation after circulatory death (DCD) expands the donor pool, and ex vivo lung perfusion (EVLP) enables graft assessment and optimization. However, its impact in this setting remains uncertain. This meta-analysis aimed to evaluate whether EVLP in DCD lungs affects graft function and short-term outcomes compared with direct transplantation.</div></div><div><h3>Methods</h3><div>Three databases were searched. The main outcome was grade 3 primary graft dysfunction (PGD). Additional outcomes included intensive care unit (ICU) and hospital length of stay (LOS), both analyzed quantitatively. Outcomes assessed qualitatively comprised short-term survival, pneumonia, and acute rejection. Random-effects models were applied to quantitative analyses.</div></div><div><h3>Results</h3><div>Five observational studies (654 patients) were included. The incidence of grade 3 PGD was comparable between EVLP and non-EVLP groups (RR 1.29; 95%CI 0.97 to 1.71; <em>p</em> = 0.08; <em>I</em>² = 12.63%). Similarly, ICU LOS (<em>p</em> = 0.12) and hospital LOS (<em>p</em> = 0.83) were also comparable. Qualitative assessment showed no apparent differences in short- and mid-term survival or in the frequency of pneumonia and acute rejection between groups.</div></div><div><h3>Conclusion</h3><div>EVLP in DCD lung transplantation was not associated with significant differences in grade 3 PGD, ICU or hospital LOS, or short- to mid-term outcomes compared with direct transplantation. Given its time and resource demands, EVLP may not be necessary for all DCD grafts; however, it remains particularly valuable for evaluating uncertain-quality lungs, where its selective use can help ensure graft safety.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100480"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146026194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-02DOI: 10.1016/j.jhlto.2025.100459
Cyrus Vahdatpour MD, MS , Katharine Clapham MD , Steven M. Kawut MD, MS , Kirk Jones Jr DO , John J. Ryan MD , Danielle Petty MD , Shannon Talbot MD , Kimberly Dumoff MD , Ellen C. Keeley MD, MS , Priti Lal MD , Andrew J. Bryant MD , Alex M. Parker MD , Jeremy A. Mazurek MD , Leonid Mirson MD , Andrew Murphy MD , Andrew Baird MD , Megan Schwietert MD , Alissa Schurr DO , Andrew Stein MD, PHD , Scott M. Hansen , Dylan Miller MD
Background
Right ventricular failure (RVF) is the primary determinant of outcomes in pulmonary hypertension (PH). Coronary microvascular dysfunction (CMD), defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF but remains poorly characterized. CMD, defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF through impaired myocardial oxygen delivery and fibrotic remodeling.
Objectives
To characterize right ventricle (RV) CMD and myocardial fibrosis in explanted human hearts and examine associations with echocardiographic and hemodynamic indices of RVF across PH subtypes.
Methods
We retrospectively analyzed 57 adult patients who underwent orthotopic heart transplantation at 3 institutions (2023-2024). Explanted hearts were classified by PH subtype: combined pre-/post-capillary PH (CpcPH, n = 24), isolated post-capillary PH (IpcPH, n = 22), and no PH (n = 11). Digital pathology quantified RV and left ventricle (LV) capillary density and interstitial fibrosis across epicardial, mid-wall, and endocardial regions. Associations with echocardiographic measures and hemodynamic parameters were assessed.
Results
A total of 57 hearts (70% male, median age 52 years) were analyzed. Median time from listing to transplantation was 1.6 months (IQR: 0.7-6.1). Mean RV capillary density was 653 ± 204 microvessels/mm2 and correlated significantly with TAPSE (ρs = 0.49, p < 0.001) and tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP) ratio (ρs = 0.33, p = 0.037). Compared to patients without PH, patterns of reduced mid-wall capillary density in PH subtypes were observed (CpcPH: β = −228 microvessels/mm2, p = 0.031; IpcPH: β = −238 microvessels/mm2, p = 0.043). Diabetes mellitus was associated with reduced LV sub-endocardial capillary density (β = −207, p = 0.006). Unadjusted analysis showed higher RV fibrosis in patients without PH (p = 0.024); however, after adjusting for clinical confounders, including heart failure etiology, this difference was not significant, highlighting the heterogenous nature of fibrosis in end-stage heart failure.
Conclusions
Capillary rarefaction is a measurable histopathologic feature in explanted RV tissue that correlates with functional indices of RV performance. Our proof-of-concept findings suggest CMD may contribute to RV systolic dysfunction independent of PH subtype.
背景：右心室衰竭（RVF）是肺动脉高压（PH）预后的主要决定因素。冠状动脉微血管功能障碍（CMD），由毛细血管稀疏和内皮功能障碍定义，可能导致裂谷热，但仍缺乏明确的特征。由毛细血管稀疏和内皮功能障碍定义的CMD可能通过心肌氧输送受损和纤维化重塑导致裂谷热。目的探讨人离体心脏右心室CMD与心肌纤维化的关系，探讨不同PH亚型RVF与超声心动图和血流动力学指标的关系。方法回顾性分析2023-2024年在3家医院接受原位心脏移植的57例成人患者。将离体心脏按PH亚型分为：合并毛细前/毛细后PH （CpcPH, n = 24）、分离毛细后PH （IpcPH, n = 22）和无PH （n = 11）。数字病理学量化右心室和左心室（LV）毛细血管密度和间质纤维化跨越心外膜、中壁和心内膜区域。评估超声心动图测量和血流动力学参数的相关性。结果共分析57例心脏，其中男性占70%，中位年龄52岁。从上市到移植的中位时间为1.6个月（IQR: 0.7-6.1）。右心室平均毛细血管密度为653±204微血管/mm2，与三尖瓣环面收缩偏移与肺动脉收缩压之比（ρs = 0.49, p < 0.001）、三尖瓣环面收缩偏移与肺动脉收缩压之比（ρs = 0.33, p = 0.037）显著相关。与非PH患者相比，PH亚型中壁毛细血管密度降低（CpcPH: β = - 228微血管/mm2， p = 0.031; IpcPH: β = - 238微血管/mm2， p = 0.043）。糖尿病与左室心内膜下毛细血管密度降低相关（β = - 207, p = 0.006）。未经校正分析显示，没有PH的患者右心室纤维化较高（p = 0.024）；然而，在调整了包括心力衰竭病因在内的临床混杂因素后，这种差异并不显著，这突出了终末期心力衰竭中纤维化的异质性。结论左心室组织的毛细血管稀疏是一个可测量的组织病理学特征，与右心室功能指标相关。我们的概念验证结果表明，CMD可能导致心室收缩功能障碍，与PH亚型无关。
{"title":"The right kind of rarefaction: Coronary microvascular remodeling in right ventricle failure","authors":"Cyrus Vahdatpour MD, MS , Katharine Clapham MD , Steven M. Kawut MD, MS , Kirk Jones Jr DO , John J. Ryan MD , Danielle Petty MD , Shannon Talbot MD , Kimberly Dumoff MD , Ellen C. Keeley MD, MS , Priti Lal MD , Andrew J. Bryant MD , Alex M. Parker MD , Jeremy A. Mazurek MD , Leonid Mirson MD , Andrew Murphy MD , Andrew Baird MD , Megan Schwietert MD , Alissa Schurr DO , Andrew Stein MD, PHD , Scott M. Hansen , Dylan Miller MD","doi":"10.1016/j.jhlto.2025.100459","DOIUrl":"10.1016/j.jhlto.2025.100459","url":null,"abstract":"<div><h3>Background</h3><div>Right ventricular failure (RVF) is the primary determinant of outcomes in pulmonary hypertension (PH). Coronary microvascular dysfunction (CMD), defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF but remains poorly characterized. CMD, defined by capillary rarefaction and endothelial dysfunction, may contribute to RVF through impaired myocardial oxygen delivery and fibrotic remodeling.</div></div><div><h3>Objectives</h3><div>To characterize right ventricle (RV) CMD and myocardial fibrosis in explanted human hearts and examine associations with echocardiographic and hemodynamic indices of RVF across PH subtypes.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed 57 adult patients who underwent orthotopic heart transplantation at 3 institutions (2023-2024). Explanted hearts were classified by PH subtype: combined pre-/post-capillary PH (CpcPH, <em>n</em> = 24), isolated post-capillary PH (IpcPH, <em>n</em> = 22), and no PH (<em>n</em> = 11). Digital pathology quantified RV and left ventricle (LV) capillary density and interstitial fibrosis across epicardial, mid-wall, and endocardial regions. Associations with echocardiographic measures and hemodynamic parameters were assessed.</div></div><div><h3>Results</h3><div>A total of 57 hearts (70% male, median age 52 years) were analyzed. Median time from listing to transplantation was 1.6 months (IQR: 0.7-6.1). Mean RV capillary density was 653 ± 204 microvessels/mm<sup>2</sup> and correlated significantly with TAPSE (ρ<sub>s</sub> = 0.49, <em>p</em> < 0.001) and tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP) ratio (ρ<sub>s</sub> = 0.33, <em>p</em> = 0.037). Compared to patients without PH, patterns of reduced mid-wall capillary density in PH subtypes were observed (CpcPH: β = −228 microvessels/mm<sup>2</sup>, <em>p</em> = 0.031; IpcPH: β = −238 microvessels/mm<sup>2</sup>, <em>p</em> = 0.043). Diabetes mellitus was associated with reduced LV sub-endocardial capillary density (β = −207, <em>p</em> = 0.006). Unadjusted analysis showed higher RV fibrosis in patients without PH (<em>p</em> = 0.024); however, after adjusting for clinical confounders, including heart failure etiology, this difference was not significant, highlighting the heterogenous nature of fibrosis in end-stage heart failure.</div></div><div><h3>Conclusions</h3><div>Capillary rarefaction is a measurable histopathologic feature in explanted RV tissue that correlates with functional indices of RV performance. Our proof-of-concept findings suggest CMD may contribute to RV systolic dysfunction independent of PH subtype.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"11 ","pages":"Article 100459"},"PeriodicalIF":0.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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